Nucleic Acid Carrier Systems Based on Polyethylenimine Conjugates for the Treatment of Metastatic Tumors

David      Schaffert; Manfred      Ogris

doi:10.2174/0929867311320280004

Abstract

Nucleic acid (NA) based drugs offer the potential of highly selective treatments for malignant diseases. They act as an initially inactive pro-drug being activated at the intended site of action, either by translation into a protein in case of plasmid DNA or through expression shutdown by interfering specifically with messenger RNA (RNAi technology). In case of already metastasized cancer, systemic treatment via the blood stream is often inevitable to reach the lesion. This makes it necessary to protect NAs from enzymatic degradation, but also to target them to the tumor with appropriate ligands. Polycationic molecules can provide such functions by condensing NAs into virus sized particles by virtue of charge interaction with the negatively charged phosphate backbone of NAs. Here we review the application of NA carrier systems based on the polycation polyethylenimine (PEI), where peptide based ligands are attached to the polycation via heterobifunctional polyethylene glycol linker molecules. Conjugate synthesis, in vitro testing and in vivo application in subcutaneous and disseminated cancer models in rodents are discussed.

Keywords: Biodegradable, cancer gene therapy, epidermal growth factor receptor, gene delivery, imaging, PEG, polyethylenimine, polyplex, targeting, tumor necrosis factor alpha.